Temperature can vary considerably in an environment. Living organisms have evolved sensory systems to detect and avoid excessive heat or cold: a behavior that is termed ‘thermotaxis’. In rare cases, animals use this ability to locate food sources in their environment. One example of such an adaptation is the female mosquito of the species Aedes aegypti. When a mosquito needs blood to produce her eggs, she becomes attracted to the body heat of warm-blooded hosts. But the range of temperatures that these mosquitoes prefer and the genes required for this behavior had not been been defined.

Now, Corfas and Vosshall have found that female Aedes aegypti are highly sensitive to differences in temperature, and are capable of heat-seeking in a range of environmental temperatures. Furthermore, by seeking out things that are warmer than their surroundings, while avoiding those that are cooler or much hotter than their host’s body temperatures, these mosquitoes tune their thermotaxis toward targets that resemble a human to feed upon.

Corfas and Vosshall also discovered that a protein called TRPA1 is required for this tuning of Aedes aegypti’s heat-seeking behavior. This protein is known to allow insects to detect chemical signals and regulate their own temperature, but it was not previously known that this protein was involved in mosquito thermotaxis. Mutant mosquitoes without the gene for TRPA1 failed to avoid high temperatures, which meant that they could no longer tell the difference between an overly hot target and a warm one that resembled their hosts.

Following on from this work, the next challenge will be to characterize all the genes, sensory organs, and neural circuits that drive mosquito heat-seeking behavior. These findings may in the future inform the design of the next generation of repellents and traps for the control of mosquito-borne diseases, such as dengue and yellow fever.

Thermotaxis is a sensory-motor behavior that guides animals toward a preferred temperature. This type of sensory navigation allows animals to avoid environments of noxious cold and heat, with the goal of remaining in physiologically suitable ambient temperatures. For ectotherms, such as most insects, thermotaxis behavior is the primary method of thermoregulation. Terrestrial invertebrates are vulnerable to temperature extremes, facing the risk of desiccation at elevated temperatures, and rapid hypothermia at low temperatures. Therefore, mechanisms to detect environmental temperatures and trigger appropriate approach or avoidance behaviors are extremely important for their survival. For instance, adult Caenorhabditis elegans worms migrate preferentially toward a specific thermal environment determined by the temperature of their cultivation (Hedgecock and Russell, 1975; Mori and Ohshima, 1995). Adult Drosophila melanogaster flies prefer a narrow range of air temperatures around 24–25°C (Sayeed and Benzer, 1996; Hamada et al., 2008) and rapidly avoid air temperatures of ~31°C (Ni et al., 2013).

Interestingly, some hematophagous (blood-feeding) arthropods have evolved a specialized mode of thermotaxis to locate endothermic (warm-blooded) hosts. Such thermophilic behavior is seen in kissing bugs [Triatoma infestans (Flores and Lazzari, 1996) and Rhodnius prolixus (Schmitz et al., 2000)], the bedbug [Cimex lectularius (Rivnai, 1931)], the tick [Ixodes ricinus (Lees, 1948)], and many species of mosquito (Clements, 1999) including Ae. aegypti, a major tropical disease-vector (Bhatt et al., 2013). Female Ae. aegypti require a vertebrate blood meal for the production of eggs, and finding a suitable warm-blooded host is therefore an essential component of reproduction. Mosquitoes use a variety of physical and chemical senses to locate hosts in their environment (Cardé, 2015). When host-seeking, these animals become strongly attracted to inanimate warm objects, eagerly probing at them as if they were hosts (Howlett, 1910).

In nature, mosquitoes thermotax in a complex thermal landscape in which ambient air temperature, host body temperature, and surrounding surface temperatures can vary widely. For mosquitoes such as Ae. aegypti, host-seeking behavior can be activated by an increase in ambient carbon dioxide (CO₂) (Majeed et al., 2014). This activation elicits flight activity (Eiras and Jepson, 1991; McMeniman et al., 2014) and results in an array of behaviors including attraction to visual stimuli (van Breugel et al., 2015) and host olfactory cues (Dekker et al., 2005; McMeniman et al., 2014), and landing on warm objects (Burgess, 1959; Eiras and Jepson, 1994; Kröber et al., 2010; Maekawa et al., 2011; McMeniman et al., 2014; van Breugel et al., 2015). Ae. aegypti flying in a wind tunnel can detect a warmed stimulus from a distance, eliciting attraction and thermotaxis (van Breugel et al., 2015).

What are the mechanisms by which animals detect thermal stimuli, and how might these be adapted for the specialized needs of heat-seeking female mosquitoes? Thermotaxis is typically initiated by thermosensitive neurons that sample environmental temperature to inform navigational decision-making. Such neurons must be equipped with molecular thermosensors capable of detecting and transducing thermal stimuli. Diverse molecular thermoreceptors have been identified in the animal kingdom, many of which are members of the transient receptor potential (TRP) superfamily of ion channels (Barbagallo and Garrity, 2015; Palkar et al., 2015). Different thermosensitive TRPs show distinct tuning spanning the thermal spectrum from noxious cold to noxious heat. Among these is TRPA1, which is a heat sensor in multiple insects, including the vinegar fly D. melanogaster and the malaria mosquito Anopheles gambiae (Hamada et al., 2008; Wang et al., 2009). Neurons in thermosensitive sensilla (Gingl et al., 2005) of An. gambiae female antennae express TRPA1 (Wang et al., 2009). In D. melanogaster, TRPA1 is expressed in internal thermosensors located in the brain, and DmelTRPA1^-/- mutants fail to avoid high air temperature in a thermal gradient (Hamada et al., 2008). Interestingly, some snakes and vampire bats express thermosensitive TRP channels in organs used to sense infrared radiation from warm-blooded prey (Gracheva et al., 2010; 2011). This raises the possibility that AaegTRPA1 may be used by mosquitoes to find hosts. Recently, a structurally distinct insect thermosensor, Gr28b, was identified in D. melanogaster (Ni et al., 2013). Gr28b, a gustatory receptor paralog, is expressed in heat-sensitive neurons of D. melanogaster aristae and is an important component of thermotaxis during rapid avoidance of heat (Ni et al., 2013). It is also highly conserved among Drosophila species (McBride et al., 2007), and has a clear ortholog in Ae. aegypti, AaegGr19 (Ni et al., 2013). A functional role for these thermosensors has never been investigated in the mosquito.

Here, we use high-resolution quantitative assays to examine the behavioral strategies underlying mosquito heat-seeking behavior. Our results show that by seeking relative warmth and avoiding both relative cool and high temperatures, female mosquitoes selectively localized to thermal stimuli that approximate warm-blooded hosts. Using genome editing, we generated mutations in the candidate thermoreceptors, AaegTRPA1 and AaegGr19. We found that TRPA1 is required for tuning mosquito thermotaxis during host-seeking. AaegTRPA1^-/- mutants lacked normal avoidance of thermal stimuli exceeding host body temperatures, resulting in a loss of preference for biologically relevant thermal stimuli that resemble hosts. This work is important because it identifies a key mechanism by which mosquitoes tune their thermosensory systems toward human body temperatures.

We previously described an assay to model heat-seeking behavior in the laboratory by monitoring mosquitoes landing on a warmed Peltier element in the context of a cage supplemented with CO₂ (Figure 1A,B) (McMeniman et al., 2014). This assay has the advantages that it is simple in design, produces robust behaviors, and enables the collection of data from large numbers of animals in a short experimental timeframe. Using this system, we can examine mosquito responses to diverse thermal stimuli and measure thermotaxis in different ambient temperature environments. We first needed to determine whether heat-seeking behavior habituates over multiple thermal stimulations. In our heat-seeking assay, Ae. aegypti mosquitoes reliably responded to 12 serial presentations of a 3-minute long 40°C stimulus over the course of more than 2.5 hr, with no evidence of habituation (Figure 1—figure supplement 1).

Figure 1 with 1 supplement see all

Download asset Open asset

Ae. aegypti can feed on a variety of hosts (Clements, 1999; Tandon and Ray, 2000) with core body temperatures ranging from ~37°C (humans) to ~40–43°C (chickens) (Richards, 1971) (Figure 1C). It is unknown whether there are minimal or maximal temperature thresholds constraining mosquito heat-seeking, and whether responses to thermal stimuli depend on the background ambient temperature.

To investigate these questions, we measured attraction to thermal stimuli produced by heating the Peltier to temperatures ranging from ambient (set to 26°C in these experiments) to 60°C (Figure 1D, E). We found that mosquitoes were highly sensitive to thermal contrast and were attracted to stimuli 2.5°C above ambient (Figure 1D–F). Furthermore, mosquito occupancy on the Peltier increased monotonically with stimulus temperatures up to 40°C. However, for higher temperature stimuli, we observed a dramatic reduction in Peltier occupancy. A 50°C stimulus resulted in approximately half as many animals on the Peltier compared to a 40°C stimulus (Figure 1D–F). Stimuli of 55°C or greater resulted in occupancy rates indistinguishable from an ambient thermal stimulus (26°C) (Figure 1D–F). Spatial analysis of mosquito occupancy on or near the Peltier revealed that while mosquitoes were still attracted to high-temperature stimuli, they populated the area peripheral to the Peltier, and strongly avoided the Peltier itself for stimuli ≥ 55°C (Figure 1F).

Female mosquitoes searching for a warm-blooded host may be responding to the absolute temperature of a stimulus or may instead be evaluating relative warmth, defined as the differential between a stimulus and background ambient temperature. To investigate the thermotaxis strategies constituting mosquito heat-seeking behavior, we conducted experiments at three ambient temperatures: 21, 26, and 31°C (Figure 2A–F). We found that Peltier occupancy for stimuli 21–40°C depended on the differential between the Peltier and ambient temperature (Figures 2B,C), rather than the absolute temperature of the Peltier (Figure 2A). For example, at all ambient temperatures tested, a stimulus 5°C above ambient was sufficient to elicit significant heat-seeking, and elicited approximately half as much Peltier occupancy as a stimulus 10°C above ambient. On the other hand, heat-seeking to targets 50–55°C was inhibited at all ambient temperatures tested (Figures 2D,F), despite the fact that the temperature differential varied widely in these situations (Figure 2E).

Figure 2 with 1 supplement see all

Download asset Open asset

These results show that Ae. aegypti thermotaxis is driven by seeking relative warmth, but restricted by an absolute upper threshold of ~50–55°C. Because female mosquitoes are attracted to relative warmth, we hypothesized that they may also avoid relative cool. This complementary behavior would serve to improve host-seeking thermotaxis. We examined mosquito responses to cooling by analyzing the rate at which animals left the Peltier when it cooled at the conclusion of a stimulus period. We found that mosquitoes left the Peltier at similar rates regardless of the absolute temperature of the stimulus (Figure 2G,H, Figure 2—figure supplement 1; based on analysis of data in Figure 1D,E), demonstrating that mosquitoes avoid relative cool during heat-seeking.

Our characterization of Ae. aegypti heat-seeking revealed multiple behavioral components contributing to selective thermotaxis during host-seeking: 1) the seeking of relative warmth; 2) the avoidance of relative cool; and 3) the avoidance of thermal stimuli exceeding host temperature. Each of these sensory-motor functions may rely on the same molecular thermosensors, or may instead use distinct thermosensors. We considered the possibility that thermoreceptors ordinarily dedicated to the behavioral thermoregulation typical of most ectotherms such as D. melanogaster, may have evolved a function in host-seeking by mosquitoes and other hematophagous arthropods. Using this reasoning, we generated AaegTRPA1^-/- mutants using zinc-finger nuclease-mediated genome editing (Figure 3A, Figure 3—figure supplement 1A).

Figure 3 with 2 supplements see all

Download asset Open asset

In addition to its function as a thermoreceptor, TRPA1 is a highly conserved chemosensor of electrophile irritants such as N-methylmaleimide (Macpherson et al., 2007; Kang et al., 2010). Using a modified capillary feeding (CAFE) assay (Ja et al., 2007) (Figure 3B), we found that wild-type Ae. aegypti mosquitoes strongly avoided consumption of N-methylmaleimide (Figure 3C), as well as the bitter compound denatonium benzoate (Figure 3D). AaegTRPA1^-/- mutants rejected denatonium benzoate (Figure 3D) but did not avoid consumption of N-methylmaleimide (Figure 3C). We interpret this result as a loss of N-methylmaleimide detection in AaegTRPA1^-/- mutants, leading to no preference between sucrose and sucrose containing N-methylmaleimide. We note that this simple CAFE assay could be used to discover additional mosquito anti-feedants to repel Ae. aegypti, beyond the two chemicals identified here.

Because TRPA1 is important in insect thermoregulation (Hamada et al., 2008), we used a modified thermal gradient assay (Sayeed and Benzer, 1996; Hamada et al., 2008) to assess thermal preference in wild-type and AaegTRPA1^-/- mutant mosquitoes (Figure 3—figure supplement 1B). AaegTRPA1^-/- mutants were impaired in avoidance of high air temperature, leading to significant mortality (Figure 3—figure supplement 1C–G). Together, these data indicate that TRPA1 has a conserved chemosensory and thermosensory function in Ae. aegypti.

We next asked if AaegTRPA1 is required for mosquito heat-seeking behavior. AaegTRPA1^-/- mutants showed normal attraction to stimuli at or below 45°C, but strikingly lacked normal avoidance of higher temperature stimuli (50°C and 55°C) (Figures 3E,F). A detailed analysis of Peltier occupancy over time revealed that AaegTRPA1^-/- mutants persisted on the Peltier during 50, 55, and 60°C stimulus presentations, whereas control animals rapidly left these high-temperature stimuli (Figure 3G). Therefore, AaegTRPA1 is not required for initial attraction to warmth but is required for normal avoidance of high-temperature stimuli that exceed host body temperature.

Because AaegTRPA1^-/- mutants retained attraction to warm stimuli, we used targeted mutagenesis to test a requirement for AaegGr19, the Ae. aegypti ortholog of Gr28b, in heat-seeking (Figure 3—figure supplement 2A,B). Although this thermosensor is required for mediating rapid avoidance of warmth in D. melanogaster (Ni et al., 2013), AaegGr19^-/- mutant mosquitoes showed no thermotaxis defects (Figure 3—figure supplement 2C). The different phenotypes of these mutations in Ae. aegypti and D. melanogaster may reflect differences in expression patterns of these genes. DmelTRPA1 is expressed in internal thermosensors of the brain (Hamada et al., 2008), while thermosensitive isoforms of DmelGr28b are expressed in peripheral heat-sensors (Ni et al., 2013). In Ae. aegypti, TRPA1 RNA is expressed in numerous tissues including the antennae (Matthews et al., 2015), where it may be associated with peripheral thermosensitive sensilla responding to rapid thermal fluctuations (Gingl et al., 2005), as it is in An. gambiae (Wang et al., 2009). The cellular expression pattern of Gr19 in Ae. aegypti is not known, but its transcript is broadly expressed (Matthews et al., 2015).

Although AaegTRPA1^-/- mutants did not show normal avoidance of high-temperature stimuli, they may still prefer host-temperature stimuli if presented with a choice. In a heat-seeking choice assay with two independently controlled Peltiers, we examined the importance of AaegTRPA1 in guiding mosquito thermotaxis in a more complex thermal landscape (Figure 4A). In this assay, mosquitoes were simultaneously presented with two thermal stimuli. When presented with two 40°C stimuli, both wild-type and mutant mosquitoes distributed equally between the Peltiers (Figure 4B), but in a choice between a 40°C and 50°C stimulus, wild-type mosquitoes strongly preferred the 40°C Peltier (Figure 4C) and avoided the 50°C Peltier (Figure 4D). Remarkably, in this choice scenario, AaegTRPA1^-/- mutants failed to avoid the 50°C Peltier, resulting in no preference for the 40°C stimulus (Figure 4 C, D, Video 1).

Figure 4

Download asset Open asset

Video 1

Download asset

We have elucidated the basic thermotaxis strategies used by mosquitoes, and revealed an important role for TRPA1 in regulating this behavior (Figure 4E). Using a quantitative thermotaxis assay, we modelled Ae. aegypti heat-seeking behavior in the laboratory. We found that mosquitoes can search for hosts in a wide range of ambient temperatures by seeking relative warmth and avoiding relative cool. Remarkably, these animals can detect a stimulus with thermal contrast as small as 2.5°C. In an outdoor environment, however, hosts are often warmer than the surrounding air but cooler than sun-warmed soil, rocks, trees, and human-made objects (Figure 4F). For this reason, diurnal mosquitoes such as Ae. aegypti are poorly served by merely thermotaxing to the hottest object available. A more optimal strategy is to search specifically for biologically relevant stimuli, and to avoid thermal stimuli exceeding host temperature, as we have observed in our laboratory models of heat-seeking. Acquiring a blood meal is an essential component of reproduction for a female Ae. aegypti mosquito. To maximize her chances of success, a female mosquito should reject ‘distracting’ stimuli that exceed host temperatures. Our results demonstrate that AaegTRPA1 is critical for this selective thermotaxis.

Mosquito heat-seeking behavior represents an excellent model system for further study of the genetics (Kang et al., 2012; Zhong et al., 2012), neuroscience (Frank et al., 2015; Liu et al., 2015), and decision-making (Luo et al., 2010) underlying thermosensation and thermotaxis. Until now, mechanistic studies of thermosensation have been largely restricted to traditional laboratory model organisms, such as domestic mice and Drosophila melanogaster flies, whose thermotaxis consists mainly of moving away from suboptimal thermal environments. Mosquitoes too, must undergo such behavioral thermoregulation, as we have found in our thermal gradient assay. However, their repertoire of thermotactic behaviors is expanded by the evolution of a specialized and highly tuned mode of thermotaxis to locate warm-blooded hosts. It may also be that these two thermotactic drives—host-seeking and thermoregulation—interact in mosquitoes. For instance, the avoidance of high-temperature stimuli during heat-seeking may be influenced by a nociceptive or thermoregulatory response independent of host-seeking behavior. It will be interesting to investigate the neural mechanisms that regulate divergent behavioral choices of thermoregulation and heat-seeking, and whether these systems are in behavioral conflict during mosquito host-seeking.

Our work identifies TRPA1 as a gene regulating mosquito avoidance of high-temperature stimuli, which we have shown to be a major behavioral component of heat-seeking. However, because both AaegTRPA1^-/- and AaegGr19^-/- mutants retain normal attraction to warmth, this aspect of heat-seeking must rely on other thermoreceptors, still to be identified. Our study shows that this attraction must be mediated either by a single thermosensor that adapts to background temperature, or multiple thermosensors each tuned to a distinct absolute threshold. During interactions with a warm-blooded host or a 50°C Peltier, mosquitoes are likely experiencing a wide range of thermal fluctuations. For instance, there can be a 10°C thermal gradient in the air within 5 mm of a 37°C stimulus or human arm (van Breugel et al., 2015). This suggests that for a mosquito standing on a warmed Peltier, the antennae, brain, thorax, forelegs, and proboscis may all be experiencing different temperatures. The temperature of mosquito tissues will also be greatly influenced by their material and geometric properties, as well as thermal conduction due to contact with the Peltier. Furthermore, convective plumes forming in the air near a vertical heated plate can be highly dynamic and turbulent in their structure, with thermal air gradients differing considerably at the bottom and top of the plate (Bejan, 2013). These features of thermal stimuli may explain why mosquitoes in our assay often appear to be differentially attracted to the bottom and top of the Peltier. Future studies characterizing this complex thermal microenvironment, and identifying the relevant thermosensory neurons and receptors will be required to define the thermal fluctuations experienced by mosquitoes during heat-seeking. Understanding the behavioral and molecular basis of thermotaxis in mosquitoes and other disease vectors (Flores and Lazzari, 1996; Schmitz et al., 2000) is of great biomedical importance. Ae. aegypti mosquitoes are potent vectors of yellow fever, chikungunya, and dengue arboviruses, resulting annually in hundreds of millions of infections (Bhatt et al., 2013). Further study of mosquito heat-seeking behavior may aid in the design of next-generation traps, repellents, and control strategies.

1. 1. Barbagallo B
   2. Garrity PA

   (2015) Temperature sensation in Drosophila

   Current Opinion in Neurobiology 34:8–13.

   https://doi.org/10.1016/j.conb.2015.01.002

   • Google Scholar
2. Book

   1. Bejan A

   (2013) Convection heat transfer: Bejan/Convection heat transfer 4e

   Hoboken, NJ, USA: John Wiley & Sons, Inc.

   https://doi.org/10.1002/9781118671627

   • Google Scholar
3. 1. Bhatt S
   2. Gething PW
   3. Brady OJ
   4. Messina JP
   5. Farlow AW
   6. Moyes CL
   7. Drake JM
   8. Brownstein JS
   9. Hoen AG
   10. Sankoh O
   11. Myers MF
   12. George DB
   13. Jaenisch T
   14. Wint GRW
   15. Simmons CP
   16. Scott TW
   17. Farrar JJ
   18. Hay SI

   (2013) The global distribution and burden of dengue

   Nature 496:504–507.

   https://doi.org/10.1038/nature12060

   • Google Scholar
4. 1. Burgess L

   (1959) Probing behaviour of Aedes aegypti (L.) in response to heat and moisture

   Nature 184:1968–1969.

   https://doi.org/10.1038/1841968a0

   • Google Scholar
5. 1. Cardé RT

   (2015) Multi-cue integration: how female mosquitoes locate a human host

   Current Biology 25:R793–R795.

   https://doi.org/10.1016/j.cub.2015.07.057

   • Google Scholar
6. Book

   1. Clements AN

   (1999)

   The biology of mosquitoes: sensory reception and behaviour

   Oxfordshire:  CABI.

   • Google Scholar
7. 1. DeGennaro M
   2. McBride CS
   3. Seeholzer L
   4. Nakagawa T
   5. Dennis EJ
   6. Goldman C
   7. Jasinskiene N
   8. James AA
   9. Vosshall LB

   (2013) Orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET

   Nature 498:487–491.

   https://doi.org/10.1038/nature12206

   • Google Scholar
8. 1. Dekker T
   2. Geier M
   3. Cardé RT

   (2005) Carbon dioxide instantly sensitizes female yellow fever mosquitoes to human skin odours

   Journal of Experimental Biology 208:2963–2972.

   https://doi.org/10.1242/jeb.01736

   • Google Scholar
9. 1. Eiras AE
   2. Jepson PC

   (1991) Host location by Aedes aegypti (Diptera: Culicidae): a wind tunnel study of chemical cues

   Bulletin of Entomological Research 81:151–160.

   https://doi.org/10.1017/S0007485300051221

   • Google Scholar
10. 1. Eiras AE
    2. Jepson PC

    (1994) Responses of female Aedes aegypti (Diptera: Culicidae) to host odours and convection currents using an olfactometer bioassay

    Bulletin of Entomological Research 84:207–211.

    https://doi.org/10.1017/S0007485300039705

    • Google Scholar
11. 1. Flores GB
    2. Lazzari CR

    (1996) The role of the antennae in Triatoma infestans: orientation towards thermal sources

    Journal of Insect Physiology 42:433–440.

    https://doi.org/10.1016/0022-1910(95)00137-9

    • Google Scholar
12. 1. Frank DD
    2. Jouandet GC
    3. Kearney PJ
    4. Macpherson LJ
    5. Gallio M

    (2015) Temperature representation in the Drosophila brain

    Nature 519:358–361.

    https://doi.org/10.1038/nature14284

    • Google Scholar
13. 1. Gingl E
    2. Hinterwirth A
    3. Tichy H

    (2005) Sensory representation of temperature in mosquito warm and cold cells

    Journal of Neurophysiology 94:176–185.

    https://doi.org/10.1152/jn.01164.2004

    • Google Scholar
14. 1. Gracheva EO
    2. Cordero-Morales JF
    3. González-Carcacía JA
    4. Ingolia NT
    5. Manno C
    6. Aranguren CI
    7. Weissman JS
    8. Julius D

    (2011) Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats

    Nature 476:88–91.

    https://doi.org/10.1038/nature10245

    • Google Scholar
15. 1. Gracheva EO
    2. Ingolia NT
    3. Kelly YM
    4. Cordero-Morales JF
    5. Hollopeter G
    6. Chesler AT
    7. Sánchez EE
    8. Perez JC
    9. Weissman JS
    10. Julius D

    (2010) Molecular basis of infrared detection by snakes

    Nature 464:1006–1011.

    https://doi.org/10.1038/nature08943

    • Google Scholar
16. 1. Hamada FN
    2. Rosenzweig M
    3. Kang K
    4. Pulver SR
    5. Ghezzi A
    6. Jegla TJ
    7. Garrity PA

    (2008) An internal thermal sensor controlling temperature preference in Drosophila

    Nature 454:217–220.

    https://doi.org/10.1038/nature07001

    • Google Scholar
17. 1. Hedgecock EM
    2. Russell RL

    (1975) Normal and mutant thermotaxis in the nematode Caenorhabditis elegans

    Proceedings of the National Academy of Sciences of the United States of America 72:4061–4065.

    https://doi.org/10.1073/pnas.72.10.4061

    • Google Scholar
18. 1. Howlett FM

    (1910) The influence of temperature upon the biting of mosquitoes

    Parasitology 3:479–484.

    https://doi.org/10.1017/S0031182000002304

    • Google Scholar
19. 1. Ja WW
    2. Carvalho GB
    3. Mak EM
    4. de la Rosa NN
    5. Fang AY
    6. Liong JC
    7. Brummel T
    8. Benzer S

    (2007) Prandiology of Drosophila and the CAFE assay

    Proceedings of the National Academy of Sciences of the United States of America 104:8253–8256.

    https://doi.org/10.1073/pnas.0702726104

    • Google Scholar
20. 1. Kang K
    2. Panzano VC
    3. Chang EC
    4. Ni L
    5. Dainis AM
    6. Jenkins AM
    7. Regna K
    8. Muskavitch MAT
    9. Garrity PA

    (2012) Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila

    Nature 481:76–80.

    https://doi.org/10.1038/nature10715

    • Google Scholar
21. 1. Kang K
    2. Pulver SR
    3. Panzano VC
    4. Chang EC
    5. Griffith LC
    6. Theobald DL
    7. Garrity PA

    (2010) Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception

    Nature 464:597–600.

    https://doi.org/10.1038/nature08848

    • Google Scholar
22. 1. Kröber T
    2. Kessler S
    3. Frei J
    4. Bourquin M
    5. Guerin PM

    (2010) An in vitro assay for testing mosquito repellents employing a warm body and carbon dioxide as a behavioral activator

    Journal of the American Mosquito Control Association 26:381–386.

    https://doi.org/10.2987/10-6044.1

    • Google Scholar
23. 1. Lees AD

    (1948)

    The sensory physiology of the sheep tick, Ixodes ricinus l

    Journal of Experimental Biology 25:145–207.

    • Google Scholar
24. 1. Liu WW
    2. Mazor O
    3. Wilson RI

    (2015) Thermosensory processing in the Drosophila brain

    Nature 519:353–357.

    https://doi.org/10.1038/nature14170

    • Google Scholar
25. 1. Luo L
    2. Gershow M
    3. Rosenzweig M
    4. Kang K
    5. Fang-Yen C
    6. Garrity PA
    7. Samuel ADT

    (2010) Navigational decision making in Drosophila thermotaxis

    Journal of Neuroscience 30:4261–4272.

    https://doi.org/10.1523/JNEUROSCI.4090-09.2010

    • Google Scholar
26. 1. Macpherson LJ
    2. Dubin AE
    3. Evans MJ
    4. Marr F
    5. Schultz PG
    6. Cravatt BF
    7. Patapoutian A

    (2007) Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines

    Nature 445:541–545.

    https://doi.org/10.1038/nature05544

    • Google Scholar
27. 1. Maekawa E
    2. Aonuma H
    3. Nelson B
    4. Yoshimura A
    5. Tokunaga F
    6. Fukumoto S
    7. Kanuka H

    (2011) The role of proboscis of the malaria vector mosquito Anopheles stephensi in host-seeking behavior

    Parasites & Vectors 4:10.

    https://doi.org/10.1186/1756-3305-4-10

    • Google Scholar
28. 1. Majeed S
    2. Hill SR
    3. Ignell R

    (2014) Impact of elevated CO₂ background levels on the host-seeking behaviour of Aedes aegypti

    Journal of Experimental Biology 217:598–604.

    https://doi.org/10.1242/jeb.092718

    • Google Scholar
29. 1. Matthews BJ
    2. McBride CS
    3. DeGennaro M
    4. Despo O
    5. Vosshall LB

    (2015)

    The neurotranscriptome of the Aedes aegypti mosquito

    BMC Genomics.

    • Google Scholar
30. 1. McBride CS
    2. Arguello JR
    3. O'Meara BC

    (2007) Five Drosophila genomes reveal nonneutral evolution and the signature of host specialization in the chemoreceptor superfamily

    Genetics 177:1395–1416.

    https://doi.org/10.1534/genetics.107.078683

    • Google Scholar
31. 1. McMeniman CJ
    2. Corfas RA
    3. Matthews BJ
    4. Ritchie SA
    5. Vosshall LB

    (2014) Multimodal integration of carbon dioxide and other sensory cues drives mosquito attraction to humans

    Cell 156:1060–1071.

    https://doi.org/10.1016/j.cell.2013.12.044

    • Google Scholar
32. 1. Mori I
    2. Ohshima Y

    (1995) Neural regulation of thermotaxis in Caenorhabditis elegans

    Nature 376:344–348.

    https://doi.org/10.1038/376344a0

    • Google Scholar
33. 1. Ni L
    2. Bronk P
    3. Chang EC
    4. Lowell AM
    5. Flam JO
    6. Panzano VC
    7. Theobald DL
    8. Griffith LC
    9. Garrity PA

    (2013) A gustatory receptor paralogue controls rapid warmth avoidance in Drosophila

    Nature 500:580–584.

    https://doi.org/10.1038/nature12390

    • Google Scholar
34. 1. Palkar R
    2. Lippoldt EK
    3. McKemy DD

    (2015) The molecular and cellular basis of thermosensation in mammals

    Current Opinion in Neurobiology 34:14–19.

    https://doi.org/10.1016/j.conb.2015.01.010

    • Google Scholar
35. 1. Richards SA

    (1971) The significance of changes in the temperature of the skin and body core of the chicken in the regulation of heat loss

    The Journal of Physiology 216:1–10.

    https://doi.org/10.1113/jphysiol.1971.sp009505

    • Google Scholar
36. 1. Rivnai E

    (1931)

    Studies in tropisms and ecology of the bed bug (Cimex lectularius l.)

    Studies in tropisms and ecology of the bed bug (Cimex lectularius l.), University of Massachusetts, Amherst.

    • Google Scholar
37. 1. Sayeed O
    2. Benzer S

    (1996) Behavioral genetics of thermosensation and hygrosensation in Drosophila

    Proceedings of the National Academy of Sciences of the United States of America 93:6079–6084.

    https://doi.org/10.1073/pnas.93.12.6079

    • Google Scholar
38. 1. Schmitz H
    2. Trenner S
    3. Hofmann MH
    4. Bleckmann H

    (2000) The ability of Rhodnius prolixus (Hemiptera; Reduviidae) to approach a thermal source solely by its infrared radiation

    Journal of Insect Physiology 46:745–751.

    https://doi.org/10.1016/S0022-1910(99)00163-8

    • Google Scholar
39. 1. Tandon N
    2. Ray S

    (2000)

    Host feeding pattern of Aedes aegypti and Aedes albopictus in Kolkata, India

    Dengue Bulletin 24:117–120.

    • Google Scholar
40. 1. van Breugel F
    2. Riffell J
    3. Fairhall A
    4. Dickinson MH

    (2015) Mosquitoes use vision to associate odor plumes with thermal targets

    Current Biology 25:2123–2129.

    https://doi.org/10.1016/j.cub.2015.06.046

    • Google Scholar
41. 1. Wang G
    2. Qiu YT
    3. Lu T
    4. Kwon H-W
    5. Jason Pitts R
    6. Van Loon JJA
    7. Takken W
    8. Zwiebel LJ

    (2009) Anopheles gambiae TRPA1 is a heat-activated channel expressed in thermosensitive sensilla of female antennae

    European Journal of Neuroscience 30:967–974.

    https://doi.org/10.1111/j.1460-9568.2009.06901.x

    • Google Scholar
42. 1. Yao Y
    2. Lian Z
    3. Liu W
    4. Shen Q

    (2008) Experimental study on physiological responses and thermal comfort under various ambient temperatures

    Physiology & Behavior 93:310–321.

    https://doi.org/10.1016/j.physbeh.2007.09.012

    • Google Scholar
43. 1. Zhong L
    2. Bellemer A
    3. Yan H
    4. Honjo K
    5. Robertson J
    6. Hwang RY
    7. Pitt GS
    8. Tracey WD

    (2012) Thermosensory and nonthermosensory isoforms of Drosophila melanogaster TRPA1 reveal heat-sensor domains of a ThermoTRP channel

    Cell Reports 1:43–55.

    https://doi.org/10.1016/j.celrep.2011.11.002

    • Google Scholar

Author details

1. Román A Corfas

   Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, United States

   Contribution

   RAC, Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article

   Competing interests

   The authors declare that no competing interests exist.

2. Leslie B Vosshall

   1. Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, United States
   2. Howard Hughes Medical Institute, The Rockefeller University, New York, United States

   Contribution

   LBV, Conception and design, Drafting or revising the article

   For correspondence

   Leslie.Vosshall@rockefeller.edu

   Competing interests

   The authors declare that no competing interests exist.

   "This ORCID iD identifies the author of this article:" 0000-0002-6060-8099

• 6,083

  views

• 894

  downloads

• 102

  citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.